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Aromatase is a key enzyme in the transformation of androgen into estrogen. Its high expression will destroy the hormonal balance in the male body, and the excessive transformation of androgen into estrogen in the body will further damage the spermatogenic function of the testis, affect the normal development of the sperm, and cause spermatogenic disturbance. Adipose tissue has a high expression of aromatase and shows high enzymatic activity and ability to convert estrogen. Adipose tissue is the most estrogen-producing nongonadal tissue in the body because of its large size, accounting for about 20% of the body mass in healthy adults. PPARγ is recognized as the key adipose differentiation in the transcriptional regulation of the transcription factor. In the process of adipocyte differentiation, PPARγ regulate the expression of aromatase. The increase of aromatase is associated with the inflammatory response in adipose tissue caused by obesity. After obesity, the increase of proinflammatory factors in adipocytes will lead to enhanced transcription of the CYP19 gene encoding aromatase in adipocytes, which in turn will lead to increased expression of aromatase in adipocytes. This article reviews the regulation of male sterility from the angle of the “obesity-inflammation-aromatase” axis.

Introduction. The advances in cerebral ischemia treatment have resulted in a larger proportion of patients get the benefits of rebuilding blood flow to the brain. Then, ischemia-reperfusion injury has emerged as a new essential problem. Dectin-1 plays an important role in cerebral ischemia-reperfusion injury by regulating the function of immune cells. Methods. C57BL/6 was blindly divided into four groups including the sham-operated group and the three different kinds of middle cerebral artery occlusion (MCAO) groups (after 6 hours, 12 hours, and 24 hours after plug removal). The protein expression levels of dectin-1, proapoptosis molecule, and antiapoptosis molecule were measured by using western blot analysis. The brain tissue was analyzed by flow cytometry to detect the M1 macrophage levels. Results. The correlation analysis of dectin-1 and infarct areas showed that there was an obviously positive correlation in between them (R = 0.9603). Dectin-1, cleaved caspase-3, and Bax increased, while antiapoptosis molecule, Bcl-2, decreased at three appropriate time points (after 6 hours, 12 hours, and 24 hours). The level of M1 macrophages in the experimental group increased after ischemia-reperfusion injury compared to the control group. Conclusions. The high expression level of dectin-1 may affect M1 macrophage polarization and brain cell apoptosis in cerebral ischemia-reperfusion injury.

Background: To explore the triggering mechanism of interstitial lung disease (ILD) by establishing the effects of immunogenic and neurogenic calcitonin gene-related peptide (CGRP) imbalance on the regulation of AQP5 expression and the repair responses to promote alveolar epithelial cell (AEC) apoptosis in pulmonary fibrosis. Methods: Newly diagnosed ILD patients (n=60) were enrolled, whoseserological levels of β-CGRP, α-CGRP, AQP5, RAMP1, and RCP were detected by ELISA. Th1 and Th2 cytokines and CD4+ and CD8+ cells were measured by flow cytometry method (FCM). In vivo, bleomycin (BLM) was set for modeling pulmonary fibrosis. The CALCA-HET model was set as a chronic pulmonary fibrosis model. Hematoxylin-eosin (H&E), immunohistochemistry, Masson's trichrome staining, and TUNEL staining was performed to assess the role of apoptosis in the injured lung. The concentrations of cytokines were determined by cytokine antibody arrays. Results: Abnormal activation of serological CD4+T lymphocytes and predominant Th2 response was established in patients with ILD. Moreover, the ratio of β-CGRP/α-CGRP was positively correlated with the increased level of AQP5 in patients with ILD. In vivo, a significant increase of AQP5 and β-CGRP at the chronic stage of pulmonary fibrosis induced by bleomycin in mice model, whereas the expression of AQP5 protein was the generally decreased in the acute alveolitis phase. Moreover, the levels of AQP5 and α-CGRP in the CALCA-HET rats were elevated. The high ratio βCGRP/α-CGRP enhanced the expression of AQP5, inhibited TGFβ1/PSmad1/Smad4 pathway, and upregulated NRF2 signal, whereas the apoptosis of alveolar epithelial cells was significantly reduced in late-stage pulmonary fibrosis. Conclusions: The high ratio of β-CGRP/α-CGRP induced predominant Th2 response and promoted AEC apoptosis through inactivation of the TGFβ1/smad1 signaling pathway and upregulation of the Nrf2 signaling in the chronic stage of pulmonary fibrosis. Funding Statement: This work was financially supported by the National Natural Science Foundation of China (no.81800070 to Xiaoting Lv and no.81871293, no.81571613 to Qicai Liu), the Joint Fund for Program of Science innovation of Fujian Province (no.2016Y9011 to Feng Gao), the Sail Foundation of Fujian Medical University (no.2016QH063 to Xiaoting Lv). Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Fujian Medical University (no. [2016]156). Consent for participation and publication the case reports was obtained. The animal experiment was approved by the Experimentation Ethics Committee on Animal Rights Protection of Fujian Medical University Animal Experiment Center (Fujian, China). During the experiments, the animals were treated in compliance with the “Guiding Opinions on the Ethical Treatments of Laboratory Animals” published by the Ministry of Science and Technology in 2006. All procedures strictly followed the National Institutes of Health guidelines for the care and use of laboratory animals.

Abdominal pain is the most common symptom of pancreatitis, but IgG4-related autoimmune pancreatitis is characterized by painless jaundice. This specific pathological phenomenon may be a breakthrough in finding a new pain mechanism. Recently, we found CGRP deficiency, plasma cell neurotropic enrichment, high basal level of prolactin (PRL) expression, and some specific neuro-antibodies in IgG4-related disease (IgG4-RD). MAG (myelin-associated glycoprotein) antibodies were detected in the serum of IgG4-RD patients by immunofluorescence (IFA) using a monkey nerve as a substrate. The specific antibodies were verified and quantified by ELISA. Cytokines were measured in tissues homogenate obtained from CGRP+/- rats by liquid suspension chip technology. A significant increase in the serum PRL level and an imbalanced ratio Th1/Th2 of IgG4-RD were established. Differential proteins in the inflammatory tissues of IgG4-RD were concentrated in the hormone-sensitive pathway. Specifically, the level of the calcitonin gene-related peptide (CGRP) was significantly decreased. Intriguingly, MAG antibodies (IgG, IgG4, and IgM) were detected by IFA and ELISA. In vivo, higher levels of PRL and Th2 cytokines were detected in CGRP+/- rats than in wild-type rats. Similarly, decreasing trends in the concentrations of IgG4-RD, Akt1 (Ser473), and STAT3 (Ser727) phosphorylation were also found in the CGRP+/- rats. Our findings indicate that the presence of CGRP-deficiency-mediated MAG antibodies is a probable molecular basis for the initial events were triggered in painless IgG4-RD via prolactin upregulation. Funding: This work was supported by a grant from the National Natural Science Foundation of China (no.81571613, 81871293 to L.Q.C., and no.81572442 to G.F.). Declaration of Interest: All authors declare that they have no conflicts of interest. Ethical Approval: This research project was approved by the Ethics Committee of the Fujian Medical University, which supervised the study.

Background: The key transformed T cells transcription factor RAG2 is regulated during inflammation to allow for the acquisition of effector T cells functions. Here, the present study was designed to investigate whether stress signals elicited by leonurine (LEO) could lead to the degradation of RAG2 through AKT signal in lung fibrosis. Methods: There were 40 female mice randomly divided into 5 groups (Group I-V): Normal group, Bleomycin (BLM), BLM LEO 50mg/kg/d, BLM LEO100mg/kg/d and BLM LEO50mg/kg/d LY294002. At 7, 14 and 28 days after modeling, pathomorphological, apoptosis, CD3 T cells, the expression of RAG2, TGFβ1 and AKT signal were detected by immunohistochemistry or western blot. Findings: Our results demonstrated T lymphocytes were reduced sharply in leonurine treated mice compared with other groups. Besides, AKT signal was greatly inhibited in BLM group and activated with leonurine treatment in Group III-IV, especially at 14th day. In addition, RAG2 was attunuated by leonurine on the 14th day- and 28th day-mold mice. Remarkably, the high-dose of leonurine did not have greater protective efficacy compared with the low-dose group of leonurine in degrees of pulmonary fibrosis, T cells inactivation and apoptosis in alveolar cells. The best dose-effect of LEO was attained in 50mg/kg/d in pulmonary fibrosis. Interpretation: The critical role of leonurine in promoting T cells inactivation by suppressing RAG2 may provide a potential therapeutic target for the intervention against pulmonary fibrosis. Funding Statement: This work was financially supported by the National Natural Science Foundation of China (no.81800070 to Xiaoting Lv and no.81871293 to Qicai Liu), the Nursery Foundation of Fujian Medical University (no.2015MP026 to Xiaoting Lv) and a grant from the Sail Foundation of Fujian Medical University (no.2016QH063 to Xiaoting Lv). Youth Research Fund Project of Fujian Provincial Health and Family Planning Commission (no.2017-1-43 to Yongping Zhu). Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: This animal experiment was approved by the Experimentation Ethics Committee on Animal Rights Protection of Fujian Medical University. During the experiments, the animals were treated in compliance with the “Guiding Opinions on the Ethical Treatments of Laboratory Animals” published by the Ministry of Science and Technology in 2006. All procedures strictly followed the National Institutes of Health guidelines for the care and use of laboratory animals.

Background: It has been observed that myeloid cells proportion increases, while lymphoid cells proportion decreases in blood of both inflammatory and cancer patients, which explains the serum concentration changes of many protein biomarkers in cancer patients versus normal controls. Methods: From literature, cancer serum and/or plasm protein biomarkers were collected and their expression patterns were examined in the microarray data of myeloid and lymphoid cells. Serum from 30 pancreatic ductal adenocarcinoma (PDAC) patients, 30 pancreatitis patients and 30 healthy volunteers, was studied using the enzyme-linked immunosorbent assay (ELISA). Findings: Among 45 protein biomarkers for PDAC, the genes expressing 15 proteins were significantly dysregulated in myeloid cells versus lymphoid cells and 13 of them, except APOA2 and THBS1, were dysregulated to the same directions as in PDAC patients versus normal controls (binomial test, P = 3.7E-3). A further comparative study was carried out on other cancers and showed significantly consistency (binomial test, P = 1.54E-02). Experimentally, we confirmed that APOA2 and THBS1 were significantly up-regulated in PDAC patients versus normal controls (Student's t test, P < 0.05) as in myeloid cells versus lymphoid cells, while there were no significant differences between PDAC and pancreatitis patients. Interpretation: We demonstrate that the ratio shifts of myeloid and lymphoid cells might lead the observed changes of many secreted protein biomarkers for cancers. Funding Statement: National Natural Science Foundation of China, Natural Science Foundation of Fujian Province, Education and Scientific Research Projects of Young and Middle-aged Teachers in Fujian Province and Fujian Medical University. Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: All subjects gave their informed consent for inclusion before they participated in the study. The study was approved by the Ethics Committee of Fujian Medical University and all experiments were performed in accordance with the approved guidelines and regulations.

To construct a restriction endonuclease based biosensor technology for PRSS1 genotyping. We designed a thiol-modified hairpin probe where the neck has EcoRI endonuclease recognition sites according to the PRSS1 gene c.410 C>T (p.T137 M) mutation and it was fixed on the gold electrode. Different charge generated by the binding of MB to phosphate groups of DNA before and after hybridization was used for distinguishing the different genotypes and quantity. This showed that the novel sensor can better distinguish the complementary sequence, single-base mismatches, and completely noncomplementary sequences, and the linear range for the logarithm was Y = –0.0242 X + 0.1574, R = 0.9912(Y = current, X = log target DNA concentration); the detection limit for DNA detection is estimated to be 50 fM.

The aim of this study was to investigate the effect of costimulation blockade with cytotoxic T-lymphocyte-associated-antigen 4-immunoglobulin (CTLA4Ig) and anti-CD40L monoclonal antibody (anti-CD40L mAb) on an experimental autoimmune myocarditis (EAM) mouse model. Characteristics of myocardial tissue were observed by hematoxylin and eosin (H&E) staining. The messenger RNA (mRNA) levels of CTLA4, CD40L, IFN-γ, and IL-4 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Serum concentrations of IFN-γ and IL-4 were determined by ELISA. After immune intervention, the inflammatory score, mRNA levels of CTLA4 and CD40L, and IFN-γ level were decreased. Furthermore, these parameters in the combinational intervention group (blockade by CTLA4Ig and anti-CD40L mAb) were significantly decreased, compared to the single intervention group (blockade by CTLA4Ig or anti-CD40L mAb). However, after costimulation, blockade serum IL-4 levels were increased. Therefore, costimulation blockade by combination CTLA4Ig and anti-CD40L mAb could more effectively inhibit the inflammatory response of EAM than single use of CTLA4Ig or anti-CD40L mAb.

Background: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. Material and methods: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. Results: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = –3.160, p = 0.042). Conclusions: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

Problem statement: More and more severe hepatitis cases reported in China are infected with HBV and the immune response of HBV will be reduced if mutations occur in the TCR, therefore it is very important to investigate the relation of T-cellular function and clinical effect by studying the function of T-cell receptor. Approach: Artificial Neural Networks (ANN) was applied to analyze basic data (the three structural of HBsAg, the ligand of HBsAg and the clinical immunological characterizations, the laboratory data, the genetypes of cationic trypsinogen gene (PRSS1) derived from 78 patients with pancreatitis and 60 normal controls were also collected. What is more, we used T-cell culture with HBV and flow cytometry to check the result of ANN predict. To examine the characteristics of T-cells capable of coexisting with the secreted HBsAg, T-cell receptor from A121T, C139S, silent mutation and normal PRSS1 gene in the patients with pancreatitis were put into research. To ensure that PRSS1 gene would affect HBsAg-specific T-cells receptor, we compared the rate of multiplication and CD4/CD8 of T-cell after culture with HBV at 0H, 12H, 24H, 36H, 48H and 72H time point. Results: The protein’s structural predicted by the ANN could specifically explain the phenomenon that the turbulence and different of anti-HBs lever of the patients with pancreatitis. The three-dimensional of the protein that consist with PRSS1 gene would accord with HBsAg. It may be one of the HBsAg-specific T-cell receptor. Result of T-cell culture also showed that different genetypes of PRSS1 had different results. In the T-cell proliferation, the groups of PRSS1 mutation (A121T and C139S) were significant lower than the group of silent mutation and normal controls and it was the same to the result of CD4/CD8. Conclusion: The ANN had been integrated into a previously published comprehensive web server to support immunology analysis and the PRSS1 gene may be the unit for HBsAg immune response.